POS0813 ALTERATION OF ILC HOMEOSTASIS MAINLY CONCERNS SALIVARY GLANDS IN PRIMARY SJÖGREN’S SYNDROME
Authors: L. Kawka, R. Felten, C. Schleiss, J. D. Fauny, P. Le Van Quyen, H. Dumortier, F. Monneaux, J. E. Gottenberg
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Little is known about the early stages leading to the autoimmune process in primary Sjögren's syndrome (pSS). Some data suggest the involvement of the innate immunity both in disease initiation and maintenance of autoimmunity in pSS, but more studies are needed to dissect the role of innate immune cell actors. Innate lymphoid cells (ILC) are a recently discovered cell population divided into three groups including type 1, 2 and 3 ILC subsets. While ILC are normally involved in the maintenance of tissue homeostasis, they can also contribute to generate tertiary ectopic lymphoid structures [1], as observed in some patients with pSS, and potentiate inflammatory processes in different chronic inflammatory diseases [2]. <h3>Objectives</h3> The aim of this study was to analyze the frequencies of ILC subsets in the peripheral blood (PB) and quantities and location in minor salivary glands (MSG) of pSS patients. <h3>Methods</h3> The frequencies of ILC subsets were analyzed in the PB of 21 pSS patients and 28 healthy controls (HC) by flow cytometry. ILC were identified as CD45+, lineage (CD1a, CD3, CD4, CD14, CD16, CD19, CD34, CD303, FcεRI)- and CD127+. Within the ILC gate, ILC1 were identified as c-kit+ and CRTH2-, ILC2 as CRTH2+, and ILC3 as c-kit+ and CRTH2–. The amounts and location of ILC subsets were studied in the MSG of 13 pSS patients and 5 controls (SC) using immunofluorescence. ILC were defined as lineage (CD3, CD14, CD19)- and CD127+ cells. The expressions of T-bet (nuclear) and CRTH2 (cytoplasmic) were used to distinguish between ILC1 (T-bet+), ILC2 (CRTH2+) and ILC3 (T-bet– and CRTH2-) subsets. <h3>Results</h3> In PB, the frequencies of total circulating ILC and ILC subsets did not differ in pSS patients compared to HC. There was a significantly higher number of circulating ILC1 in pSS patients with positive anti-SSA antibodies (p=0.03) and a lower number of circulating ILC3 in pSS patients with glandular swelling (p=0.01). The proportions of ILC subsets in PB did not correlate with systemic disease activity measured by ClinESSDAI. Most of the ILC identified in MSG of pSS patients were ILC3 (91.1%). The amount of ILC3 was higher in tissues with lymphocytic infiltrates compared to non-infiltrated tissues in pSS patients (p=0.0002) and to normal glandular tissues in SC (p=0.0005). No difference was observed when comparing the quantity of ILC1 and ILC2 in the MSG between pSS patients and SC. ILC3 were preferentially located at the periphery of the infiltrates and were inversely correlated with the surface of T/B lymphocyte infiltrates (r=-0.42, p=0.002). ILC3 were inversely correlated with time since diagnosis (r=-0.69, p= 0.01). <h3>Conclusion</h3> Alteration of ILC homeostasis mainly concerns salivary glands in pSS. The majority of ILC in MSG is composed by ILC3, located at the periphery of lymphocytic infiltrates. ILC3 are more abundant in smaller infiltrates and in recently diagnosed pSS patients. ILC3 might play a pathogenic role in the development of T and B lymphocyte infiltrates in the early stages of pSS. <h3>References</h3> [1]Meier D, Bornmann C, Chappaz S, Schmutz S, Otten LA, Ceredig R, et al. Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced survival of lymphoid-tissue-inducer cells. Immunity. mai 2007;26(5):643‑54. [2]Ebbo M, Crinier A, Vély F, Vivier E. Innate lymphoid cells: major players in inflammatory diseases. Nat Rev Immunol. nov 2017;17(11):665‑78. <h3>Acknowledgements</h3> We would like to thank all patients who have participated to the study. <h3>Disclosure of Interests</h3> None Declared.